Chronic olanzapine administration in rats: Effect of route of administration on weight, food intake and body composition

Atypical antipsychotics are associated with increased risk of weight gain, and researchers have turned to rodent models to better understand underlying mechanisms. Weight gain has been inconsistent in these studies though, possibly related to the rapid metabolism of antipsychotics in rodents. This study investigates olanzapine, an atypical antipsychotic with high liability for weight gain in humans, administered to rats by continuous infusion via osmotic minipump versus daily subcutaneous (s.c.) or intraperitoneal (i.p.) injections. We examined body weight, food intake and body composition for olanzapine (7.5 mg/kg/day) versus placebo (n = 8/group) in female Sprague–Dawley rats using the 3 routes of administration over 14 days. For olanzapine treated animals, weight gain was significantly greater in the minipump sample compared to both s.c. and i.p. injections. Twice as many animals (i.e. 75%) gained ≥ 7% body weight compared to either daily s.c. or i.p. injections. Olanzapine treated animals consumed more kilocalories than vehicle, and the minipump group consumed more than either daily injection group, although the difference with the s.c. sample was nonsignificant. Significantly more visceral fat was amassed in olanzapine treated animals versus vehicle, again greatest in the minipump sample, although differences between groups did not reach significance. The magnitude of increase across all groups fits with other evidence suggesting change in body composition may represent a more sensitive measure than body weight in assessing antipsychotic related changes. We conclude that the rodent model is tenable in evaluating the effects of antipsychotics on weight/body composition.

► Antipsychotic-related weight gain in rodents does not mirror humans.
► Rapid antipsychotic metabolism may contribute to this.
► Olanzapine via minipump produces greater weight gain than daily injections.
► In addition to weight, visceral adiposity warrants evaluation.